Possible enhancement of the first-pass metabolism of prenacetin by grape juice in Chinese subjects

AIMS: This serendipitous study revealed an unexpected effect of Jufeng grape juice on the CYP1A2-mediated metabolism of phenacetin. Investigation of the inhibition of CYP1A2 by grapefruit juice was involved but a translation error led to the grape juice substitution.

METHODS: Twelve healthy subjects took a single oral dose of phenacetin (900 mg) on two randomized occasions together with 200 ml water or grape juice. Plasma phenacetin and paracetamol concentrations were assessed by h.p.l.c.

RESULTS: Ingestion of grape juice was associated with reduced plasma phenacetin concentrations, while paracetamol levels were unaffected. Paracetamol to phenacetin AUC ratios increased from 13.9+/-3.1 to 24.3+/-3.8 after ingestion of grape juice.

CONCLUSIONS: These findings suggest enhanced first-pass metabolism of phenacetin, due to CYP1A2 activation by grape juice or to desaturation of CYP1A2 isoenzymes secondary to a slower rate of phenacetin absorption.